The hallmark of type 1 diabetes is leukocyte infiltration into the pancreatic islets of Langerhans, or insulitis. Although detection of autoantibodies against islet beta-cell proteins is generally taken as an indirect indicator of insulitis, a non-invasive means to directly view leukocyte infiltration would have important applications for diabetologists, perhaps permitting earlier and more discriminatory diagnosis, more accurate staging and more rational stratification. Data on mouse models of type 1 diabetes indicate that magnetic resource imaging of the distribution of Monochrystalline Iron Oxide Nanoparticles (MION) after intravenous injection permits quantitation of various microvascular parameters (blood flow, blood volume, extravasatism, etc) in vivo in real time, and that certain of these are detectably altered in inflamed islets. This promising finding, plus the fact that MIONs are currently in clinical use for early detection of cancer, begs for the extrapolation of this strategy to human type 1 diabetes patients, the goal of this component of the program, Project 4. Therefore, we intend to: 1. Identify the optimal conditions for imaging the human pancreas with Combidex -- in low-risk prediabetic, high-risk prediabetic and recent-onset diabetes patients. 2. Examine certain classes of non-typical diabetes patients -- antibody-negative first-degree relatives, slow progressors or individuals with latent autoimmune diabetes in adults, or LADA. 3. Follow disease course in a subset of patients, correlating imaging results with more classical clinical indices of disease progression, such as autoantibody titers and first-phase insulin release. Successful establishment of this imaging method for human diabetes patients should provide an entirely novel "window" on disease processes. We should obtain new information about the natural history of type 1 diabetes in humans, and may develop a valuable means to diagnose/stage/stratify disease earlier and with greater discrimination.